Population Council Research that makes a difference

Council scientists decided to develop a ring that releases NES/EE in a dose of 150/15 µg per day on a three-weeks-in, one-week-out usage schedule. (The ring is inserted for three weeks, then removed for one week to allow menstruation.) In order to register a product with the US Food and Drug Administration, a large-scale Phase 3 study must be carried out with rings made using a mass-manufacturing method. Consequently, a contract manufacturer (QPharma, Malmö, Sweden) has been identified to make the rings.

Two major efforts have occurred. First, the contract manufacturer has developed a manufacturing method to mass produce the rings required for the Phase 3 study. The rings were produced by the contract manufacturer and analyzed in Council laboratories to ensure that they release the proper dose of drugs. Second, a Phase 3 study of the ring is well underway to more precisely evaluate the effectiveness and side effects of the mass-manufactured ring. Over 2,000 women have been enrolled, and the treatment portion of the trial is scheduled for completion by the end of December 2008.

The rings used in the original Phase 2 dose-ranging and schedule variation studies were fabricated at the Center for Biomedical Research using different materials and different sources of materials than those used in the mass-manufactured rings for the Phase 3 trial. For this reason, a pharmacokinetic (PK) trial was required as a nested study within the pivotal Phase 3 clinical trial. The goal of the nested PK study was to determine the amount of Nestorone taken up into the bloodstream with use of the ring over a course of three cycles.

Three clinics participated in the nested PK study, with an additional 13 clinics coming on stream in mid-2006. A total of 1,280 women used the ring for one year, and the study ran until late 2008. Study results will form the basis of an application to the US Food and Drug Administration for approval of the drug, which will lead to its registration and introduction into family planning programs.

"The one-year contraceptive ring: A technology in development," brochure (PDF) 
Publication date: 2006


Contraceptive vaginal rings releasing Nestorone® and ethinylestradiol: A 1-year dose-finding trial (abstract) 
Sivin,Irving; Mishell,Daniel R.,Jr.; Alvarez,Francisco; Brache,Vivian; Elomaa,Kaisa; Lahteenmaki,Pekka; Massai,Rebeca; Miranda,Patricia; Croxatto,Horacio B.; Dean,Catherine; Small,Margaret; Nash,Harold A.; Jackanicz,Theodore M.
Contraception 71(2): 122-129
Publication date: 2005


Serum Nestorone® and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen-ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen (abstract) 
Fraser,Ian S.; Weisberg,Edith; Brache,Vivian; Alvarez,Francisco; Massai,Rebeca; Mishell,Daniel R.,Jr.; Apter,Dan; Gale,Judi; Tsong,Yun-yen; Sivin,Irving
Contraception 72(1): 40-45
Publication date: 2005


New delivery systems in contraception: Vaginal rings (abstract) 
Johansson,Elof D.B.; Sitruk-Ware,Regine
American Journal of Obstetrics and Gynecology 190(suppl 1): S54-S59
Publication date: 2004


Nestorone®: Clinical applications for contraception and HRT (abstract) 
Sitruk-Ware,Regine; Small,Margaret; Kumar,Narender; Tsong,Yun-yen; Sundaram,Kalyan; Jackanicz,Theodore M.
Steroids 68(10-13): 907-913
Publication date: 2003